European Review for Medical and Pharmacological Sciences
Current practice and potential strategy in
diagnosing COVID-19
D.-Y. WAN1, X.-Y. LUO1, W. DONG2, Z.-W. ZHANG2
The West China College of Medicine, Sichuan University, Chengdu, China
1
Department of Intensive Care Medicine, West China Hospital, Sichuan University, Chengdu, China
2
D.-Y. Wan, X.-Y. Luo, and W. Dong contributed equally in writing this article
Abstract. – OBJECTIVE: To summarize the
current practice and potential strategy in diag-
nosing coronavirus disease 2019 (COVID-19).
MATERIALS AND METHODS: PubMed, Web
of Science were systematically searched us-
ing terms including “COVID-19”, “SARS-CoV-2”
and “2019-nCoV”. After removing duplicates, we
then identified articles, letters and commentar-
ies regarding diagnosing COVID-19.
RESULTS: Here we summarized relatively ma-
ture diagnostic methods like nuclear acid test
and computed tomography. Besides, new aspects
regarding these detection methods like suitable
specimens for nuclear acid test, possible use of
18F-FDG PET/CT were also reported. Especially,
we also presented several novel techniques for di-
agnosing COVID-19 like lung ultrasound.
CONCLUSIONS: Chinese Clinical Guidance for
COVID-19 Pneumonia Diagnosis and Treatment
(7th edition) by National Health Commission is
recommended to follow as it provides detailed
diagnostic procedures using currently available
tools. We suggest clinicians further explore the
saliva’s utility as a specimen for nuclear acid test
and the use of lung ultrasound.
Key Words:
COVID-19, Diagnosis, Nuclear acid test, CT image,
IgM-IgG test.
Introduction
In December 2019, a new type of coronavirus
broke out in Wuhan and spread rapidly in China.
Later, other regions around the world soon report-
ed confirmed cases. In February 2020, the coro-
navirus study group of the International Com-
mittee on Taxonomy of Virus named the virus
Severe Acute Respiratory Syndrome Coronavirus
2 (SARS-CoV-2). As of March 16, 2020, the virus
has infected more than 80,000 people in China
and more than 90,000 in other countries, posing a
significant threat to global public health security1.
4548 Corresponding Author: Zhong-Wei Zhang, MD; e-mail: 716461751@qq.com
2020; 24: 4548-4553
SARS-CoV-2 is a single-stranded RNA virus
that belongs to the coronavirus β genus, struc-
tural proteins of which include S proteins, N
proteins, M proteins, and E proteins2. Its infecting
procedure shares a great similarity with SARS-
CoV2,3. By binding to the angiotensin-converting
enzyme 2 receptor on the outside membrane, the
virus gradually fuses into the host cell, causing
great damage to its original function.
This novel coronavirus is mainly transmitted
by aerosol like respiratory droplets generated
during coughing and sneezing by symptomatic
patients4. Caution is due here since asymptom-
atic patients in incubation period can also help
its transmission. Besides, the median incubation
period is 6.4 days, ranging from 2.1 days to 11.1
days5. This long period can cause great trouble in
containing this widely-spread pandemic. Failing
in restraining international transportation result-
ed in a surge in the number of suspected and
confirmed infections globally. To slow down its
spread and eventually contain it, accurate, rapid
and convenient screening and diagnostic methods
are of great significance. Here we summarized
current practice and potential strategies in diag-
nosing COVID-19. This brief review may be of
help to clinicians who work in fever clinics or
perform screening in public areas.
Diagnosis
Clinical Features
At the early onset of this pandemic disease, a
report from Hubei initially summarized clinical
characteristics of 138 patients6. The authors found
that the most common symptoms were fever
(98.6%), fatigue (69.6%) and dry cough (59.4%)
and that elderly patients were more likely to prog-
ress into a severe stage and later be transferred
to intensive care units. Recently, Spiteri et al7
 Current practice and potential strategy in diagnosing COVID-19
reported 20 cases of COVID-2019 in European
region, clinical manifestations of which share
some similarity with those of patients reported
from Wuhan. Fever was also found to be the most
common syndrome (n=20; 52.63%), followed by
cough (n=14; 36.84%), weakness (n=8; 21.05%)
and headache (n=6; 15.79%).
Laboratory Examination
Blood samples of suspected patients were rou-
tinely collected when they entered the hospital.
Indexes like white blood cell count and concen-
trations of C-reactive protein were then detected.
Lippi et al8 summarized several abnormal labora-
tory manifestations in COVID-19 infected peo-
ple. They recommended some possible indexes
for identifying suspected patients like increase in
CRP concentration and decrease in both leuko-
cytes and lymphocytes.
Nuclear Acid Test
Real time reverse-transcription poly chain re-
action (RT-PCR), the usual detection method for
common respiratory virus is also the primary
diagnostic means for 2019-nCoV9,10. However,
current positive rates of this test can vary greatly,
depending on types of the specimens and gene
fragments used.
Liu et al11 collected laboratory results of 4,880
cases from Jan 22 to Feb 14 in Renmin Hospital
of Wuhan University and found that the positive
rate of tests based on nucleocapsid protein se-
quence was 40.81%. But in Wang et al12, positive
rate of test targeting at open reading form 1ab
was reported to be 32.27%. As for different spec-
imens, things were even more complicated. Re-
cently, several researches investigated the biodis-
tribution of COVID-19 in different tissues. It was
found that, apart from excretion from respiratory
tract, the virus can also be detected in blood12,
tears13, oral fluids14 and feces12,15,16. However, tests
on feces, blood, tears only have positive rates
measuring 29% (n=44), 1% (n=3) and 5% (n=1)
respectively, which cannot satisfy the needs for
accurate diagnosis12,13. Fortunately, saliva had a
remarkable performance in serving as samples.
In a diagnostic study, self-collected saliva of
91.7% of patients generated positive outcomes14.
Despite the high positive rates, procedures for
sampling saliva also involve less exposure chanc-
es, further guaranteeing clinicians’ safety. How-
ever, the limited cases involved restrain its usage
in practical settings. Thus, more relevant studies
are urgently needed.
One of the limitations of RT-PCR is the
time-consuming procedures involved in prac-
tical settings. Besides, its accuracy also needs
great improvements. To satisfy the growing
needs for a rapid and accurate NAT method for
COVID-19, several researches were done and
some of them generated rather promising out-
comes. Pfefferle et al17 described a new method,
cobas 6800 in detail. This integrated technol-
ogy performed on a high-throughput platform
allows less hands-on time while maintaining
fast and reliable results. In another study, Chan
et al18 illustrated three novel real-time RT-
PCR methods targeting at the RNA-dependent
RNA polymerase, envelope and nucleocapsid
genes from SARS-CoV-2. Of notice, this newly
developed assay, entitled COVID-2019-RdRp/
Hel, had a relatively lower limit of detection.
Combined with the fact that saliva contained
higher concentration of viral load14, this tech-
nique may significantly reduce the false nega-
tive numbers and therefore limit the spread of
SARS-CoV-2. Apart from real time RT-PCR,
fluorescence quantitative PCR (FQ-PCR) was
also proposed19. The report declared their expe-
rience of applying high-throughput sequencing
to further the inconclusive result generated by
the FQ-PCR.
Imaging Features
Computed Tomography
Though NAT is considered as the gold stan-
dard for COVID-19, abundant false positive
cases indicate that another complimentary tool
is needed. Computed tomography (CT) then
acts as such tool20,21. This method was basically
available in all sorts of medical institutions and
can generate outcomes rapidly. Bilateral ground
glass opacity was discovered in 98% of the
suspected cases in one study22. A more detailed
article reporting imaging features of different
disease stages was available recently23. Patchy
ground glass opacities in the peripheral areas
with partial consolidation in the center were
found in most of the common patients. Larger
areas of opacities and consolidations can be
discovered in severe patients. Of note, while one
lesion can be absorbed under correct medical
care, another novel lesion may soon appear in
another area. This phenomenon may inform us
of the necessity of repeated CT scanning for
closely evaluating disease progression.
4549
 D.-Y. Wan, X.-Y. Luo, W. Dong, Z.-W. Zhang
To evaluate its accuracy in identifying pa-
tients with COVID-19 from suspected groups,
a report of 1,014 cases analyzed the correlation
of chest CT and NAT24. Researchers discovered
that the positive rate of CT test was much higher
than that of RT-PCR. Attention is needed when
clinicians interpret the results. 52% of 308 pa-
tients with negative RT-PCR but positive CT
results were not considered as confirmed cases
at last. That is to say, CT test is more likely to
generate false positive outcomes, which may
result in waste of medical resources. Worse still,
the error can hardly be estimated as suspected
patients with positive CT images may eventually
be affected in hospitals full of genuine patients.
Li et al20 specially demonstrated its defect in
differentiating COVID-19 from other viruses,
partially explaining the high false positive rate.
Besides, the accuracy of CT test depends greatly
on the radiologist. In the research by Ai et al24,
we may notice that an expert with 12 years of
experience was involved in the interpretation.
Lung Ultrasound
Apart from CT, lung ultrasound (US) was also
recommended recently25. It was once reported
to be superior to standard CT for evaluation of
pneumonia or respiratory distress syndrome26.
Peng et al27 performed lung US on 20 patients and
summarized five main clinical findings, including
thickening of the irregular pleural line. Besides, a
strong connection between ultrasonography find-
ings and the disease stages was also reported.
This indicates its great use in dynamically mon-
itoring COVID-19 progression. Chinese Critical
Ultrasound Study Group published Critical-Ul-
trasound-based Recommendations on Severe
COVID-19 recently, in which lung US findings
and relevant managements were described in
detail28.
18
F-FDG PET/CT
18
F-FDG PET/CT is a technology that can re-
flect changes in metabolic and functional states in
patients while observing pathogenic structures of
lesion sites. Qin et al29 reported clinical findings
gained by 18F-FDG PET/CT. Ground-glass opaci-
ties showed a high tracer uptake of 18F-FDG. Be-
sides, the image firstly suggested that COVID-19
may cause lymphadenitis. However, a letter
against its use for diagnosis was published30. One
reason is the complex procedure needed would be
4550
unpractical in most clinical settings, and the other
reason is the risk of disease spreading due to the
long period it takes.
Immunological Examinations
When combined together, detection methods
mentioned above are of help in identifying in-
fected patients in clinical settings. Nevertheless,
containing COVID-19 demands detection meth-
ods with large scale screening and field detection
ability, neither of which is satisfied by etiological
detection or medical imaging technology.
Fortunately, a qualified method was success-
fully developed31. This novel technique uses lat-
eral flow immunoassay to detect IgM and IgG
antibodies against COVID-19 in human blood
samples simultaneously. Apart from the short
period, both sensitivity and specificity are also
remarkably high. It may suggest its potential use
as a diagnostic tool for rapid screening in public
area like airport, station, etc. Of notice, this tech-
nique can only tell whether the subject is infected
recently instead of the current conditions.
Prospects
The paragraph above illustrated the results ob-
tained from different specimens. Current samples
used in clinical settings are mainly nasal or pha-
ryngeal swabs, which usually generate positive
rates only measuring 40% or so11. However, we
may notice a study discovering that saliva showed
a remarkable performance in RT-PCR tests14. We
therefore recommend researchers to focus on this
utility and further explore the accuracy of NAT
detecting this specimen.
Notably, though blood and tears did not seem
to be of interest during diagnostic procedures,
they were reported to have a strong relationship
with specific clinical manifestations. Chen et
al32 reported a group of 58 cases. Patients with
detectable viral RNA in blood all gradually de-
veloped to a severe stage. The only sample of
tear that yielded positive results was collected
from a patient with conjunctivitis13. Nevertheless,
inherent defects in both studies resulted in these
unconvincing statements. More researches are
still needed for further illustrations.
Besides, lung US also seemed to be a prom-
ising technology available in most clinical set-
tings with ability to provide rapid outcomes25.
Of notice, this technique was also reported to
 Current practice and potential strategy in diagnosing COVID-19
have several limits27. For example, it can not
detect pathological changes that are deep in the
lung and therefore CT would still be of neces-
sity. 18F-FDG PET/CT proposed by Qin et al29
may not be available in clinical use due to its
inherent defects. However, as it can reveal ab-
normal metabolic and functional manifestations
of COVID-19, it may serve as an investigation
tool for the time being.
As for the immunological test described, we
believe that it can be of great help in countries
with urgent needs for rapid screening to contain
the spread of COVID-19. Of note again, IgM-IgG
test is not able to test the current health condition
of patients, it can only inform us whether the pa-
tient was infected recently31. Thus, it should only
be used in field detection to identify suspected or
confirmed patients and may not serve as an indi-
cator in discharge criteria.
We here recommend the Chinese Clinical
Guidance for COVID-19 Pneumonia Diagno-
sis and Treatment (7th edition) published by
National Health Commission, in which diag-
nosis procedures were given in great detail21.
Briefly, the procedures can be divided into two
separate parts. To determine whether one is a
suspected patient, epidemiological history or
clinical symptoms are needed. Exposure history
involves any form of body contact with con-
firmed cases within 14 days and clinical features
include symptoms like fever, CT images with
signs mentioned above and laboratory examina-
tion showing decrease in both leukocytes and
lymphocytes. One with exposure history can be
considered as a suspected patient if any two of
the clinical features show up, but only when an
exposure-free patient represents all three clini-
cal features can he be suspected. Later, samples
from a suspected patient will run NAT and
serology test. When any of NAT and IgM-IgG
test generates positive result, he or she will be
confirmed and receive further treatments.
Lately, America, Australia, Iran and Italy all
reported a tremendous increase in confirmed
cases recently, among which Italy is now the
most serious region attacked by SARS-CoV-21.
There was a growing concern that COVID-19
will rapidly spread the European continent
among the public, which caused great panic
and influenced the economic hugely33. Timely
and firm measures shall be taken to contain
the COVID-19 before it causes more damaging
results. To achieve this goal, timely diagnosis is
of great significance. We hope this review will
help those who are fighting at the frontline and
the containment of this pandemic.
Conflict of Interest
The Authors declare that they have no conflict of interests.
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